Use of adrenomedullin derivatives for molecular imaging of pulmonary circulation.
Currently, there is no low-molecular-weight agent for imaging of the pulmonary circulation. Adrenomedullin (AM) is a peptide predominantly cleared by the pulmonary circulation through specific endothelial receptors. We developed human AM derivatives radiolabeled with 99mTc and evaluated their biodistribution, plasma kinetics, and utility as pulmonary vascular imaging agents.


METHODS
Two derivatives radiolabeled with 99mTc were evaluated: the natural cyclic form of the peptide, to which the chelator diethylenetriaminepentaacetic acid was added (C-DTPA-AM), and the linear form, which allows direct labeling (L-AM). The compounds were injected into dogs, and the activities of the tracers in blood and in organs were determined with a nuclear medicine camera. Single-pass pulmonary clearance was measured by the indicator dilution technique. The capacity to image perfusion defects was evaluated after surgical pulmonary artery ligation.


RESULTS
Both derivatives were rapidly cleared from plasma, with elimination half-lives of 42 and 32 min for C-DTPA-AM and L-AM, respectively. The lungs retained most of the activity after 30 min; this activity was higher (P = 0.02) for L-AM (42% +/- 5% [mean +/- SEM]) than for C-DTPA-AM (27% +/- 1%). Lung activity slowly declined over time but was maintained after 2 h at approximately 20% for both tracers. The single-pass pulmonary clearance of plasma L-AM was 414 +/- 85 mL/min. There was a higher level of urinary excretion of L-AM than of C-DTPA-AM. After pulmonary artery ligation, perfusion defects were easily detectable by external imaging.


CONCLUSIONS
AM derivatives are promising compounds for molecular imaging of the pulmonary circulation. L-AM displayed higher levels of initial lung retention and of kidney excretion.
Harel
François
F
Research Center, Montreal Heart Institute/Université de Montréal, Montreal, Quebec, Canada.
Fu
Yan
Y
Nguyen
Quang Trinh
QT
Letourneau
Myriam
M
Perrault
Louis P
LP
Caron
Alexandre
A
Fournier
Alain
A
Dupuis
Jocelyn
J
D053607:Adrenomedullin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D004285:Dogs; D006207:Half-Life; D006801:Humans; D007267:Injections; D007700:Kinetics; D008657:Metabolic Clearance Rate; D004369:Pentetic Acid / Q000737:chemistry; D055420:Perfusion Imaging / Q000379:methods*; D011651:Pulmonary Artery / Q000473:pathology / Q000503:physiopathology; D011652:Pulmonary Circulation; D014018:Tissue Distribution
D002614:Chelating Agents; D053607:Adrenomedullin; D004369:Pentetic Acid